This project uses imaging science techniques to analyze many types of biological, clinical and biomedical images. Current research focuses on two general areas: (1) the structural biology of macromolecules using image processing of electron micrographs and NMR spectroscopy and (2) biomedical and laboratory imaging. (1) The Imaging Sciences Laboratory has a major collaborative research effort with the Institutes involving the use of image processing techniques and advanced computational techniques in structural biology to analyze electron micrographs and NMR spectra with the goal of determining macromolecular structures. Recent efforts have concentrated on the 3D reconstruction, analysis and interpretation of the structures of icosahedral virus capsids. Ongoing research involves analyses of structures related to herpesvirus as well as other icosahedral virus capsids. This year we determined that absolute handedness of herpesvirus capsids and have analyzed the morphogenesis of the procapsid to the mature capsid. We have been developing computational tools for biomolecular NMR structure determination. We are actively supporting the community of intramural and extramural users of the Xplor-NIH biomolecular structure determination program. Further development of this program has progressed support has continued in the following four areas: (a) the Python and TCL scripting interfaces have been enhanced; (b) we have added functionality for convenient parallel computations involving ensembles of molecular structures, appropriate for studies which include dynamical effects; (c) we have extended the descriptions of dipolar coupling experiments such that the orientational tensor can be refined simultaneously, along with atomic coordinates; (d) we have successfully demonstrated a facility for the automatic assignment of NOE spectra. (2) The Imaging Sciences Laboratory has a commitment to providing computational and engineering expertise to a variety of clinical and biomedical activities at NIH. Specifically, PET, ultrasound, CT, MRI, EPR, microscopy, imaging in cancer research, and imaging related to neural disfunction have been supported in a number of ways. To support scientific research in the NIH intramural program, CIT has made significant major progress in the development of a platform-independent, n-dimensional, general-purpose, extensible image processing and visualization program written in the JAVA programming language. The MIPAV (Medical Image Processing Analysis and Visualization) application enables quantitative analysis and visualization of medical images of numerous modalities. It has been used to analyze tumors for Diagnostic Radiology, assisted in longitudinal studies in collaboration with NIDCR, analysis of MRI images for NIMH, and has been used by NCI for the analysis of 2D and 3D microscopic samples. Most recently we have (in collaboration with NEI) adapted MIPAV to be used as a surgeon's tool to assist in the evaluation of a treatment protocol for macular degeneration.